Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study
Vergote, Ignace; Van Nieuwenhuysen, Els; O'Cearbhaill, Roisin Eet al.
2023 • In Journal of Clinical Oncology, p. 2300720
[en] [en] PURPOSE: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC).
METHODS: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR).
RESULTS: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E).
CONCLUSION: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.
Disciplines :
Oncology
Author, co-author :
Vergote, Ignace ; Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven Cancer Institute, Leuven, Belgium
Van Nieuwenhuysen, Els; Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven Cancer Institute, Leuven, Belgium
O'Cearbhaill, Roisin E ; Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY
Westermann, Anneke ; Dutch Gynaecological Oncology Group, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Lorusso, Domenica ; Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Catholic University of Sacred Heart, Rome, Italy
Ghamande, Sharad; Department of Obstetrics and Gynecology, Augusta University, Augusta, GA
Collins, Dearbhaile C ; Department of Medical Oncology, Cancer Trials Ireland, Cork University Hospital, Cork, Ireland
Banerjee, Susana ; Royal Marsden National Health Service Foundation Trust, Institute of Cancer Research, London, United Kingdom
Mathews, Cara A ; Program in Women's Oncology, Women & Infants Hospital, Legorreta Cancer Center at Alpert Medical School of Brown University, Providence, RI
Gennigens, Christine ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Cibula, David ; Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
Tewari, Krishnansu S ; University of California, Irvine, CA
Madsen, Kristine; Centre for Cancer and Organ Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
Köse, Fatih; Baskent University, Ankara, Turkey
Jackson, Amanda L; Department of Obstetrics and Gynecology, University of Cincinnati Cancer Center, Cincinnati, OH
Boere, Ingrid A ; Erasmus MC Cancer Institute, Rotterdam, the Netherlands
Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study
Publication date :
31 August 2023
Journal title :
Journal of Clinical Oncology
ISSN :
0732-183X
eISSN :
1527-7755
Publisher :
American Society of Clinical Oncology (ASCO), United States
